Adherence to Hidradenitis Suppurativa Treatment.

Hidradenitis suppurativa (HS) is a chronic, debilitating skin condition that requires multimodal treatment. Adherence remains a significant challenge for many patients due to complex nature of treatment, thus presenting a barrier to management success. This review summarizes the current literature on the factors associated with adherence to medications, and lifestyle behaviors in patients with HS and proposes strategies to improve adherence. In February 2023, a systematic literature search was conducted by two independent authors on PubMed and EMBASE for articles from 2000 to 2023 on hidradenitis suppurativa adherence. A total of 21 articles met inclusion/exclusion criteria for this review. Of the studies, 11 addressed systemic medication adherence, 3 addressed topical medication adherence, 2 addressed both systemic and topical medication adherence, and 5 addressed lifestyle/behavioral modification adherence. The generalizability of results was limited by differences in study design, outcome measures, and sample size. English-only articles with full texts were used. The most reported reasons for non-adherence included presence of side effects, cost of medications, low efficacy, and unclear instructions. Proposed strategies to improve adherence in HS patients include management of side effects, use of reminder systems, improved patient education, patient support groups, aid of family and caregivers, personalization of the medication regimen, and regular follow-ups with patients. PROSPERO Registration Number: CRD42023488549.

Perspectives of Emergency Medicine Physicians on Hidradenitis Suppurativa Care.

Introduction: Hidradenitis suppurativa (HS) is a chronic skin condition that often requires acute care during periods of flares, with many patients visiting the emergency department over 5 times before receiving a proper diagnosis. However, little is known about emergency medicine (EM) providers' experiences and knowledge of HS management. Methods: In this study, an anonymous survey was distributed to EM providers to identify knowledge and practice gaps in HS care. Results: The results showed that most respondents lacked confidence in HS diagnosis and management, especially in knowing available treatment options and managing patients with moderate to severe HS. Attendings were more confident than non-attendings in diagnosing and managing HS, and providers who saw more HS patients per month were more confident in referring patients to appropriate specialists. Over 80% of respondents referred HS patients to dermatology, which is an important initial step in HS management. Conclusion: The study highlights the importance of educating EM providers in HS recognition, timely referral to dermatology, and initial management to improve quality of life among patients and mitigate disease progression.

Emergence of amoxicillin resistance and identification of novel mutations of the pbp1A gene in Helicobacter pylori in Vietnam.

BACKGROUND: Amoxicillin-resistant Helicobacter pylori (H. pylori) strains seem to have increased over time in Vietnam. This threatens the effectiveness of H. pylori eradication therapies with this antibiotic. This study aimed to investigate the prevalence of primary resistance of H. pylori to amoxicillin and to assess its association with pbp1A point mutations in Vietnamese patients. MATERIALS AND METHODS: Naive patients who presented with dyspepsia undergoing upper gastrointestinal endoscopy were recruited. Rapid urease tests and PCR assays were used to diagnose H. pylori infection. Amoxicillin susceptibility was examined by E-tests. Molecular detection of the mutant pbp1A gene conferring amoxicillin resistance was carried out by real-time PCR followed by direct sequencing of the PCR products. Phylogenetic analyses were performed using the Tamura-Nei genetic distance model and the neighbor-joining tree building method. RESULTS: There were 308 patients (46.1% men and 53.9% women, p = 0.190) with H. pylori infection. The mean age of the patients was 40.5 ± 11.4 years, ranging from 18 to 74 years old. The E-test was used to determine the susceptibility to amoxicillin (minimum inhibitory concentration (MIC) ≤ 0.125 µg/ml) in 101 isolates, among which the rate of primarily resistant strains to amoxicillin was 25.7%. Then, 270 sequences of pbp1A gene fragments were analysed. There were 77 amino acid substitution positions investigated, spanning amino acids 310-596, with the proportion varying from 0.4 to 100%. Seven amino acid changes were significantly different between amoxicillin-sensitive (AmoxS) and amoxicillin-resistant (AmoxR) samples, including Phe366 to Leu (p <  0.001), Ser414 to Arg (p <  0.001), Glu/Asn464-465 (p = 0.009), Val469 to Met (p = 0.021), Phe473 to Val (p <  0.001), Asp479 to Glu (p = 0.044), and Ser/Ala/Gly595-596 (p = 0.001). Phylogenetic analyses suggested that other molecular mechanisms might contribute to amoxicillin resistance in H. pylori in addition to the alterations in PBP1A. CONCLUSIONS: We reported the emergence of amoxicillin-resistant Helicobacter pylori strains in Vietnam and new mutations statistically associated with this antimicrobial resistance. Additional studies are necessary to identify the mechanisms contributing to this resistance in Vietnam.

Air pollution caused by phthalates and cyclic siloxanes in Hanoi, Vietnam: Levels, distribution characteristics, and implications for inhalation exposure.

Contamination status and distribution characteristics of ten phthalic acid esters (PAEs) and three cyclic volatile methyl siloxanes (CSs) were determined in the air (gas and particle) samples collected from indoor and outdoor spaces of several chemistry laboratories, offices, and homes from urban area of Hanoi, the capital city of Vietnam. Air concentrations of Σ10PAEs (median 688; range 142-2390 ng m-3) and Σ3CSs (171; not detected-1100 ng m-3) in the indoor air samples were significantly higher than those measured in the outdoor ones (Σ10PAEs: 161; 34.1-515 ng m-3 and Σ3CSs: 43.2; not detected-258 ng m-3), partly suggesting the predominance of indoor emission sources of these substances. There were significant positive correlations in total air concentrations of phthalates and siloxanes between the indoor and outdoor air samples. The most predominant phthalates were diethyl-, di-n-butyl-, diisobutyl-, and di(2-ethylhexyl) phthalate. For siloxanes, D5 and D6 were more abundant than D4 in most samples. Except for di(2-ethylhexyl)- and di-n-octyl phthalate in some locations, almost all the compounds were likely associated with gas phase than particle phase. Daily intake doses of airborne phthalates and siloxanes, and non-cancer and cancer risks of selected phthalates were estimated for different exposure groups such as adults, children, and university subjects (e.g., laboratory staff and students), indicating relatively low levels of risk.

Metastasis of cholangiocarcinoma is promoted by extended high-mannose glycans.

Membrane-bound oligosaccharides form the interfacial boundary between the cell and its environment, mediating processes such as adhesion and signaling. These structures can undergo dynamic changes in composition and expression based on cell type, external stimuli, and genetic factors. Glycosylation, therefore, is a promising target of therapeutic interventions for presently incurable forms of advanced cancer. Here, we show that cholangiocarcinoma metastasis is characterized by down-regulation of the Golgi α-mannosidase I coding gene MAN1A1, leading to elevation of extended high-mannose glycans with terminating α-1,2-mannose residues. Subsequent reshaping of the glycome by inhibiting α-mannosidase I resulted in significantly higher migratory and invasive capabilities while masking cell surface mannosylation suppressed metastasis-related phenotypes. Exclusive elucidation of differentially expressed membrane glycoproteins and molecular modeling suggested that extended high-mannose glycosylation at the helical domain of transferrin receptor protein 1 promotes conformational changes that improve noncovalent interaction energies and lead to enhancement of cell migration in metastatic cholangiocarcinoma. The results provide support that α-1,2-mannosylated N-glycans present on cancer cell membrane proteins may serve as therapeutic targets for preventing metastasis.

Micronutrients in Atopic Dermatitis: A Systematic Review.

Objective: The pathophysiology of atopic dermatitis (AD) involves a complex interplay between immune system dysfunction, genetics, and environmental factors. It is well known that nutritional status is essential to a proper functioning immune system, leading to a highly debated question regarding the role of dietary factors in the pathogenesis of AD. Food allergies and elimination diets have been broadly studied in atopy; however, less consideration has been given to how vitamins, minerals, and other micronutrients influence the risk for AD and severity of symptoms. This systematic review discusses evidence on how various micronutrients, including vitamins (C, E, and D) and trace minerals (zinc, selenium, iron, copper, magnesium, and strontium) are associated with AD, and how supplementation influence disease severity. Design: A systematic search was conducted to identify the role that oral micronutrients have on AD. The authors reviewed 49 studies herein. Results: While there are weak associations between vitamins C or E and AD, there is sufficient evidence to suggest that vitamin D supplementation provides benefit in AD patients. Deficiency of selenium and zinc may exacerbate AD. Current reports are not sufficient to confidently discern the role of other vitamins and trace minerals on AD. Conclusions: Though oral micronutrients may play a role in AD, the current literature is limited, and there is a need for more comprehensive randomized controlled trials (RCTs) to truly decipher the role between oral micronutrients and AD.

Neurosurgical Oncology in Vietnam.

BACKGROUND: In conjunction with Vietnam's unparalleled economic growth over the past 20 years, our scope of neurosurgical interventions has considerably diversified throughout this time period. METHODS: Although still appreciably limited, healthcare resources and infrastructure have expanded and shifted the focus within neurosurgery at Ho Chi Minh City's Cho Ray Hospital from head trauma (which remains highly prevalent) to an equal proportion of elective cases for vascular lesions, tumors, and degenerative spine disease. Arguably the most significant progress throughout the new millennium has been achieved in the realm of neurosurgical oncology. RESULTS: About 1000 craniotomies are performed annually for brain tumors at our institution, most of which are for lower-grade lesions that result in excellent surgical outcomes. We continue to strive to improve the standard of care for patients with malignant brain tumors, as the first multidisciplinary neuro-oncology care team was founded recently in 2016. CONCLUSIONS: This article is the first in the English neurosurgical literature to report on the current state and outcomes of neuro-oncology in Vietnam, as we highlight our experiences in caring for patients with brain tumors at Cho Ray Hospital.

Pain and Itch Are Dual Burdens in Atopic Dermatitis.

BACKGROUND: Despite being widely reported by patients with atopic dermatitis (AD), pain symptoms, unlike itch, have not been widely assessed. OBJECTIVE: The aim of the study was to understand the distinct pain symptoms in patients with AD. METHODS: Responses from an anonymous questionnaire were collected from our eczema clinic (in-person survey) and collaboration with Global Parents for Eczema Research Group and the National Eczema Association (online survey) to assess skin pain among patients with AD 5 years and older. Eczema Area and Severity Index was measured in the clinic cohort to correlate with pain symptoms. CONCLUSIONS: In our international cohort of 103 patients with AD, 78% reported concomitant pain and itch. The greatest pain burden occurred on the hands (odds ratio [OR], 0.77), perioral region (OR, 0.74), and toes (OR, 0.7), corresponding to regions with the greatest sensory nerve density. Pain was most commonly described as "burning" and "stinging," particularly when lesions were red, cracked, and dry. Its presence significantly interfered with sleep, leisure activities, and activities of daily living. Among the clinic cohort, we observed a strong Spearman correlation between objective Eczema Area and Severity Index score and subjective skin pain. It is imperative that clinicians understand patients' unique pain burden to best evaluate clinical severity and quality-of-life interference.

New and emerging targeted systemic therapies: a new era for atopic dermatitis.

PURPOSE: This is a review of emerging targeted, systemic therapies for atopic dermatitis (AD). The information presented aims to provide dermatologists with updated therapeutic options, stimulate academic interest, and spark future research. MATERIAL AND METHODS: Extensive search of ClinicalTrials.gov, the National Eczema Association, and PubMed was performed for clinical trials examining the effect of emerging targeted, systemic therapies in patients with AD. Results were included if they demonstrated efficacy in reversing AD symptoms. Studies that did not demonstrate clinical benefit were excluded. RESULTS: A number of emerging systemic agents targeting specific mediators involved in the pathogenesis of AD were found. These targets include IL-4, IL-13, IgE, B-cells, IL-5, IL-31, JAK-STAT, SYK, IL-6, PDE-4, IL-12, IL-17, IL-23, IL-22, H4R, NKR1, κOR, TSLP, PPAR-γ, and DGLA. Treatment of AD patients with these therapies has, in many cases, led to statistically significant improvements in clinical severity scores and patient-reported outcomes. CONCLUSIONS: While multiple agents have demonstrated efficacy, only dupilumab is currently approved for adults with AD. Large-scale, randomized, placebo-controlled, double-blind trials, especially in children, are needed. As we enter the dawn of targeted therapy for AD, a comprehensive clinical trial registry is needed to facilitate data pooling and comparison among international registries.

Oncolytic Reactivation of KSHV as a Therapeutic Approach for Primary Effusion Lymphoma.

Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma caused by Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Currently, treatment options for patients with PEL are limited. Oncolytic viruses have been engineered as anticancer agents and have recently shown increased therapeutic promise. Similarly, lytic activation of endogenous viruses from latently infected tumor cells can also be applied as a cancer therapy. In theory, such a therapeutic strategy would induce oncolysis by viral replication, while simultaneously stimulating an immune response to viral lytic cycle antigens. We examined the combination of the FDA-approved drug ingenol-3-angelate (PEP005) with epigenetic drugs as a rational therapeutic approach for KSHV-mediated malignancies. JQ1, a bromodomain and extra terminal (BET) protein inhibitor, in combination with PEP005, not only robustly induced KSHV lytic replication, but also inhibited IL6 production from PEL cells. Using the dosages of these agents that were found to be effective in reactivating HIV (as a means to clear latent virus with highly active antiretroviral therapy), we were able to inhibit PEL growth in vitro and delay tumor growth in a PEL xenograft tumor model. KSHV reactivation was mediated by activation of the NF-κB pathway by PEP005, which led to increased occupancy of RNA polymerase II onto the KSHV genome. RNA-sequencing analysis further revealed cellular targets of PEP005, JQ1, and the synergistic effects of both. Thus, combination of PEP005 with a BET inhibitor may be considered as a rational therapeutic approach for the treatment of PEL. Mol Cancer Ther; 16(11); 2627-38. ©2017 AACR.

MEK inhibitors and their potential in the treatment of advanced melanoma: the advantages of combination therapy.

The treatment of melanoma has improved markedly over the last several years with the advent of more targeted therapies. Unfortunately, complex compensation mechanisms, such as those of the mitogen-activated protein kinase (MAPK) pathway, have limited the clinical benefit of these treatments. Recently, a better understanding of melanoma resistance mechanisms has given way to intelligently designed multidrug regimes. Herein, we review the extensive pathways of BRAF inhibitor (vemurafenib and dabrafenib) resistance. We also review the advantages of dual therapy, including the addition of an MEK inhibitor (cobimetinib or trametinib), which has proven to increase progression-free survival when compared to BRAF inhibitor monotherapy. Finally, this review touches on future treatment strategies that are being developed for advanced melanoma, including the possibility of triple therapy with immune checkpoint inhibitors and the work on optimizing sequential therapy.

Endothelial ß-Catenin Signaling Is Required for Maintaining Adult Blood-Brain Barrier Integrity and Central Nervous System Homeostasis.

BACKGROUND: The blood-brain barrier (BBB) formed by brain endothelial cells interconnected by tight junctions is essential for the homeostasis of the central nervous system. Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB. METHODS AND RESULTS: Using a mouse model with tamoxifen-inducible endothelial cell-restricted disruption of ctnnb1 (iCKO), we show here that endothelial ß-catenin signaling is essential for maintaining BBB integrity and central nervous system homeostasis in adult mice. The iCKO mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and central nervous system inflammation, and all had postictal death. Disruption of endothelial ß-catenin induced BBB breakdown and downregulation of the specific tight junction proteins claudin-1 and -3 in adult brain endothelial cells. The clinical relevance of the data is indicated by the observation of decreased expression of claudin-1 and nuclear ß-catenin in brain endothelial cells of hemorrhagic lesions of hemorrhagic stroke patients. CONCLUSIONS: These results demonstrate the prerequisite role of endothelial ß-catenin in maintaining the integrity of adult BBB. The results suggest that BBB dysfunction secondary to defective ß-catenin transcription activity is a key pathogenic factor in hemorrhagic stroke, seizure activity, and central nervous system inflammation.

100% Complete response rate in patients with cutaneous metastatic melanoma treated with intralesional interleukin (IL)-2, imiquimod, and topical retinoid combination therapy: results of a case series.

BACKGROUND: Patients with cutaneous melanoma metastases have experienced excellent responses to intralesional interleukin (IL)-2. This has led to its recent inclusion into the US National Comprehensive Cancer Network guidelines for management of cutaneous melanoma metastases. Despite this, intralesional IL-2 has not been highlighted in the US literature nor have US physicians adopted it. OBJECTIVE: We sought to evaluate the effectiveness of intralesional IL-2 combined with topical imiquimod and retinoid for treatment of cutaneous metastatic melanoma. METHODS: A retrospective case series of 11 patients with cutaneous metastatic melanoma were treated with intralesional IL-2 combined with topical imiquimod and retinoid. RESULTS: A 100% complete local response rate with long-term follow-up (average of 24 months) was seen in all 11 patients treated with this proposed regimen. Biopsy specimens of treated sites confirmed absence of malignant cells. The most common treatment-related adverse event was rigors. LIMITATIONS: Small number of patients, retrospective review of charts, and lack of a comparison group were limitations. CONCLUSION: Intralesional IL-2 administered concomitantly with topical imiquimod and a retinoid cream is a promising therapeutic option for managing cutaneous melanoma metastases. The regimen was well tolerated and should be considered as a reasonable alternative to surgical excision.